Although there is abundant evidence in man and animals that immunologic vigor declines with age, the role of T and B lymphocytes in the immunology of aging is not understood. Furthermore, there is virtually no direct information regarding the genetic control of any parameter of aging. Preliminary observations indicate that the Ir gene controlling the response to antigen E is associated with the second locus of HLA. In all probability other antigens will bear a similar relationship to the HLA system. By studying the immune responsiveness and HLA haplotypes in families which include four generations, it will be possible to define aging genetically. The use of antigen E and other ethical antigens will serve as in vitro probes (blast transformation) for Ir genes in selected HLA population. Measurement of T and B cells, immunoglobulin levels and autoantibody production in this population will provide additional information toward a better understanding of the control of age-associated immune pathology. In addition, these studies will permit us to examine the relationship between genetic control of immune responsiveness, HLA markers and susceptibility of resistance to disease. BIBLIOGRAPHIC REFERENCES: Yunis, E.J., Amos, D.B. and Blumenthal, M.N.: Genetic Mapping of IrE Outside of HL-A-MLR-S Complex. Transplant. Proc. 7:49, (Suppl. 1), 1975. Yunis, E.J., Fernandes, G. and Greenberg, L.J.: Immune Deficiency, Autoimmunity and Aging. Birth Defects: Original Article Series 11:185, 1975.